title: Computational design of the sequence and structure of a protein-binding peptide.
abstract: The de novo design of protein-binding peptides is challenging because it requires the identification of both a sequence and a backbone conformation favorable for binding. We used a computational strategy that iterates between structure and sequence optimization to redesign the C-terminal portion of the RGS14 GoLoco motif peptide so that it adopts a new conformation when bound to Gα(i1). An X-ray crystal structure of the redesigned complex closely matches the computational model, with a backbone root-mean-square deviation of 1.1 Å.
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599-7260, USA.
authors.forename: Deanne W
authors.initials: DW
authors.lastname: Sammond
authors.forename: Dustin E
authors.initials: DE
authors.lastname: Bosch
authors.forename: Glenn L
authors.initials: GL
authors.lastname: Butterfoss
authors.forename: Carrie
authors.initials: C
authors.lastname: Purbeck
authors.forename: Mischa
authors.initials: M
authors.lastname: Machius
authors.forename: David P
authors.initials: DP
authors.lastname: Siderovski
authors.forename: Brian
authors.initials: B
authors.lastname: Kuhlman
mesh_terms: D019295:Computational Biology; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D010455:Peptides; D019206:GTP-Binding Protein alpha Subunits, Gi-Go